Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants

Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants
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DOI:
10.1097/00008571-200401000-00001
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发表时间:
2004-01-01
期刊:
PHARMACOGENETICS
影响因子:
--
通讯作者:
Nebert, DW
Nebert, DW
中科院分区:
其他
文献类型:
--
作者:
Nelson, DR;Zeldin, DC;Nebert, DW

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目的在私人和公共部门完成小鼠和人类基因组序列的研究,促进了这两个物种在多个水平上的比较。本文对细胞色素P450(CYP)基因超家族进行了综述。这是我们第一次有能力比较两种哺乳动物的全套CYP基因。将老鼠作为模式哺乳动物,并作为人类生物学的替代品,假设两者之间存在合理的相似性。方法用数据挖掘的方法寻找小鼠和人类的全部CYP序列,其中包括小鼠的102个假定功能基因和88个伪基因,以及人类的57个假定功能基因和58个伪基因。结果与结论7个CYP基因簇在小鼠中扩增出72个功能基因,而在人类中仅有27个,同时存在许多伪基因,推测在其他基因超家族簇中也会出现这种现象。所有假基因序列的完整鉴定可能在临床上很重要,因为这些高度相似的外显子中的一些可能会干扰基于PCR的基因分型分析。我们提出了四类CYP假基因的命名程序,并鼓励各基因命名委员会认真考虑采用和应用这一假基因命名系统。(C)2004年,里平科特·威廉姆斯·威尔金斯。
Objectives Completion of both the mouse and human genome sequences in the private and public sectors has prompted comparison between the two species at multiple levels. This review summarizes the cytochrome P450 (CYP) gene superfamily. For the first time, we have the ability to compare complete sets of CYP genes from two mammals. Use of the mouse as a model mammal, and as a surrogate for human biology, assumes reasonable similarity between the two. It is therefore of interest to catalog the genetic similarities and differences, and to clarify the limits of extrapolation from mouse to human.Methods Data-mining methods have been used to find all the mouse and human CYP sequences; this includes 102 putatively functional genes and 88 pseudogenes in the mouse, and 57 putatively functional genes and 58 pseudogenes in the human. Comparison is made between all these genes, especially the seven main CYP gene clusters.Results and conclusions The seven CYP clusters are greatly expanded in the mouse with 72 functional genes versus only 27 in the human, while many pseudogenes are present; presumably this phenomenon will be seen in many other gene superfamily clusters. Complete identification of all pseudogene sequences is likely to be clinically important, because some of these highly similar exons can interfere with PCR-based genotyping assays. A naming procedure for each of four categories of CYP pseudogenes is proposed, and we encourage various gene nomenclature committees to consider seriously the adoption and application of this pseudogene nomenclature system. (C) 2004 Lippincott Williams Wilkins.